Myocardial infarction is caused by an abrupt occlusion of a coronary artery resulting in interruption of circulation to the affected muscle. It is now known that most myocardial infarctions occur when a blockage in the coronary artery ulcerates creating a milieu for clot formation. The cause of this change in plaque morphology (ulceration) is unclear but may be related to an inflammatory cascade or some other yet to be determined “trigger”. The term now used to describe this transition in coronary lesion morphology preceding myocardial infarction is “vulnerable plaque”. Rarely coronary artery occlusion may be caused by clot from a remote location (paradoxical embolic event from a deep venous thrombosis or migration of clot from left ventricular thrombosis). Even less common is embolic septic emboli from valve infections or spontaneous coronary dissection.
In either of the foregoing scenarios, once the blockage occurs, the portions of the heart muscle nourished by the effected artery becomes ischemic and cell death or “necrosis” begins within minutes. If the blockage can be opened quickly, e.g., generally in less than 15 minutes, the infarcted region may continue to perform without degraded function. Accordingly, great urgency is required in resolving a blockage once it is formed.
As is well-known, most tissue in the human body originates from undifferentiated cells known as stem cells. These fundamental building blocks differentiate into specific target parenchymal tissue based on hormonal and other signals. Scientific evidence suggests that stems cells or endothelial progenitor cells injected into a target tissue will differentiate into the cell line of that specific tissue. This feature is of particular interest in treating conditions involving organs that cannot regenerate, such as the heart.
It has been postulated that it may be possible to improve function of an infarcted region of heart muscle by injecting stem cells or endothelial progenitor cells into the effected region as soon as the blockage is resolved. Unfortunately, conventional methods of separating stem cells from autologous material, such as bone marrow, typically require several hours of laboratory processing and culturing—far too long to provide effective near-term treatment for an acute myocardial infarction.
Since stem cells and endothelial progenitor cells have been observed in the circulation, it also may be beneficial to inject mediators of stem cell mobilization, migration and attachment. For example, Granulocyte-stimulating factor (GSF) and stem cell factor (SCF) that mobilize stem cells from the bone marrow may be introduced into circulation. Vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 (SDF-1) causes release of homing factors that may bring circulating progenitor cells to the infracted myocardium to assist in repair.
In addition, it has been observed that blood vessels within ischemic tissue tend to dilate. Accordingly, even where direct injection of stem cells into the cardiac vasculature is possible, such a process would be impractical after the blockage has been opened, as the dilated myocardial blood vessels would permit the injected stem cells to be swept through the vessels so quickly that only a small percentage of the stem cells could embed in the tissue.
In view of the aforementioned limitations of previously-known systems and methods, it would be desirable to provide apparatus and methods for treating myocardial infarction by controlling the rate of blood flow through the vessels of infarcted tissue during introduction of stem cells into the region.
It would further be desirable to provide apparatus and methods for treating myocardial infarction by occluding the coronary sinus, and then injecting stem cells into a coronary artery.
It also would be desirable to provide apparatus and methods for treating myocardial infarction by inducing retrograde blood flow within the coronary sinus, and then injecting stems cells into the coronary sinus.
It still further would be desirable to provide apparatus and methods for treating myocardial infarction using direct injections of autologous material, e.g., such as bone marrow aspirants, into the cardiac vasculature to promote tissue regeneration in an infarcted region of the myocardium.
It also would be desirable to provide apparatus and methods for inducing retrograde blood flow within the coronary venous vasculature that do not require an external power source, but instead may be driven by naturally-occurring pressure gradients within the patient's body.